Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation

Anthony Brehm, Patrick Geraghty, Michael A Campos, Itsaso Garcia-Arcos, Abdoulaye Jules Dabo, Adam Gaffney, Edward Eden, Xian Cheng Jiang, Jeanine D'Armiento, Robert Foronjy

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Phospholipid transfer protein (PLTP) regulates phospholipid transport in the circulation and is highly expressed within the lung epithelium, where it is secreted into the alveolar space. Since PLTP expression is increased in chronic obstructive pulmonary disease (COPD), this study aimed to determine how PLTP affects lung signaling and inflammation. Despite its increased expression, PLTP activity decreased by 80% in COPD bronchoalveolar lavage fluid (BALF) due to serine protease cleavage, primarily by cathepsin G. Likewise, PLTP BALF activity levels decreased by 20 and 40% in smoke-exposed mice and in the media of smoke-treated small airway epithelial (SAE) cells, respectively. To assess how PLTP affected inflammatory responses in a lung injury model, PLTP siRNA or recombinant protein was administered to the lungs of mice prior to LPS challenge. Silencing PLTP at baseline caused a 68% increase in inflammatory cell infiltration, a 120 and 340% increase in ERK and NF-κB activation, and increased MMP-9, IL1β, and IFN-γ levels after LPS treatment by 39, 140, and 190%, respectively. Conversely, PLTP protein administration countered these effects in this model. Thus, these findings establish a novel anti-inflammatory function of PLTP in the lung and suggest that proteolytic cleavage of PLTP by cathepsin G may enhance the injurious inflammatory responses that occur in COPD.

Original languageEnglish
Pages (from-to)2318-2331
Number of pages14
JournalFASEB Journal
Volume28
Issue number5
DOIs
StatePublished - Jan 1 2014

Fingerprint

Phospholipid Transfer Proteins
Cathepsin G
Pneumonia
Degradation
Pulmonary diseases
Chronic Obstructive Pulmonary Disease
Bronchoalveolar Lavage Fluid
Smoke
Lung
Fluids
Lung Injury
Serine Proteases
Matrix Metalloproteinases
Recombinant Proteins
Infiltration
Small Interfering RNA
Phospholipids
Anti-Inflammatory Agents
Epithelium

Keywords

  • Lipopolysaccharide
  • Lung
  • Protease
  • Signaling

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Brehm, A., Geraghty, P., Campos, M. A., Garcia-Arcos, I., Dabo, A. J., Gaffney, A., ... Foronjy, R. (2014). Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation. FASEB Journal, 28(5), 2318-2331. https://doi.org/10.1096/fj.13-246843

Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation. / Brehm, Anthony; Geraghty, Patrick; Campos, Michael A; Garcia-Arcos, Itsaso; Dabo, Abdoulaye Jules; Gaffney, Adam; Eden, Edward; Jiang, Xian Cheng; D'Armiento, Jeanine; Foronjy, Robert.

In: FASEB Journal, Vol. 28, No. 5, 01.01.2014, p. 2318-2331.

Research output: Contribution to journalArticle

Brehm, A, Geraghty, P, Campos, MA, Garcia-Arcos, I, Dabo, AJ, Gaffney, A, Eden, E, Jiang, XC, D'Armiento, J & Foronjy, R 2014, 'Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation', FASEB Journal, vol. 28, no. 5, pp. 2318-2331. https://doi.org/10.1096/fj.13-246843
Brehm, Anthony ; Geraghty, Patrick ; Campos, Michael A ; Garcia-Arcos, Itsaso ; Dabo, Abdoulaye Jules ; Gaffney, Adam ; Eden, Edward ; Jiang, Xian Cheng ; D'Armiento, Jeanine ; Foronjy, Robert. / Cathepsin G degradation of phospholipid transfer protein (PLTP) augments pulmonary inflammation. In: FASEB Journal. 2014 ; Vol. 28, No. 5. pp. 2318-2331.
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